The invention relates to a drug delivery treatment system and method of making the system and method of treating the eye.
Most ocular treatments require frequent topical administration of drugs to the tissues of the ocular cavity.
When medication must be applied topically to the eye, one common form of treatment is the use of liquid drops. The liquid drop form is extremely easy to use as the patient merely self-administers the liquid through an eye dropper or dispenser which includes an eye drop extension end. However, a substantial disadvantage of the liquid form is that the medication or lubricating solution rapidly drains from the ocular cavity into the nasal cavity through an opening called the punctum. Further, the liquid may simply evaporate from the eye.
Thus, with the use of liquid treatments, a continuous prolonged delivery of medication is not achieved, and the exact dosage is unpredictable as liquid drains out of the eye. Even with intermittent administration, the liquid treatment will continue to rapidly wash out of the eye, and the continued problem of unpredictability of dosage remains. Further, continuous administration of liquid is not only inconvenient, but may be dangerous.
Several systems shown in U.S. patents provide large ocular inserts to deliver drug to an eye continuously. Certain inserts disperse the drug and require removal of the carrier of the drug once the drug has been delivered. However, U.S. Pat. Nos. 3,845,201; 4,164,559 and 4,179,497 show various inserts in the form of large pellets which dispense drug over a period of time and eventually are completely eroded, and thus do not require removal after drug delivery.
These inserts have certain advantages over the liquid treatments as more predictable dosage is obtained as there is a continuous dispensing of the drug over a period of time without rapid washout. Thus, the unitary ocular inserts provide predictable dosage over a period of time without the requirement of repeated applications as required with liquid treatments.
However, there are certain disadvantages which accompany the use of large unitary ocular inserts. These unitary inserts must be carefully placed under the eyelid, and require special care and special insert devices for insertion. Difficulties in patient education for inserting these in compliance with proper technique have prevented their widespread use.
In an attempt to address the problems of liquid treatments and ocular inserts, U.S. Pat. Nos. 3,914,402; 4,001,388 and 4,115,554 all to Shell, show ophthalmic forms which include a suspension of solid particles from 10 to 300 microns in largest dimension in a liquid medium. The liquid medium in the Shell patents is used exclusively as a carrier for suspending the particles and delivering the particles to the eye. The Shell dosage form alleviates certain problems associated with ocular inserts, including the complication of insertion and requirement for special insertion devices. However, the liquid carrier in Shell does not include drug therein, and therefore, the liquid does not deliver drug to the ocular environment. Only the minute particles can be relied on for drug delivery. Treatment with the Shell patent system depends on the chance of the particles becoming lodged in the eye tissue, as the liquid delivers no drug. Further, as no drug is included in the liquid, all the medication which is limited to inclusion in the particles, could feasibly wash out of the eye with the particles through the punctum which is about 0.5 mm in diameter. Thus, Shell may effectively deliver no drug at all to the ocular environment, as the particles may drain out of the eye prior to release of the medication from the particles.
Although Shell asserts that the particles do not drain from the ocular cavity through the punctum, in practice if the particles are substantially smaller in diameter than the punctum, these particles will wash and drain out of the eye in the normal course of drainage of the suspension liquid through the natural duct system of the ocular cavity. As the Particles in Shell are delivered in a liquid suspension, the excess liquid delivered to the eye would naturally drain through the punctum. Further, liquid contact alone with the eye would provide no medication to the ocular environment as the liquid is free of medication.
U.S. Pat No. 3,826,258 to Abraham shows a gradual release medicine carrier. Abraham addresses topical treatment of the eye using capsules which are dropped into the eye. Similar to the Shell system, the liquid carrier in the Abraham patent is used merely to suspend the capsules and deliver the capsules to the eye. Abraham neither shows nor suggests including drug in the liquid carrier solution.
Thus, an object of the present invention is to provide a drug delivery system, a method of making the drug delivery system and a method of treatment which includes the advantages of drug solution treatments, insert treatments and suspension treatments.
It is a further object to provide a treatment system method which delivers a dependable dosage or amount of treatment media to the eye. It is a further object to provide an ophthalmic treatment system easily administered to the eye which will remain in the ocular cavity over a period of time.
It is yet another object to provide a system which provides prolonged drug delivery as well as instant delivery of drug to the eye.
These and other objects are achieved by providing an ophthalmic drug delivery system which includes at least one particle of bioerodible material. The particle or particles are suspended in one of a liquid carrier and an ointment carrier containing ophthalmic drug and having a pH acceptable to the eye.
The drug delivery system provides prolonged delivery of drug to the eye as drug in the solution is absorbed into the particles of bioerodible material prior to administration and/or after administration to the eye. The drug absorbed in the bioerodible material will be released over a period of time as the particles erode in the ocular environment. Further, an instant delivery of drug to the eye is provided by the drug in the liquid or ointment carrier. Thus, where instant delivery is needed, the liquid carrier provides instant release of drug and the particles provide prolonged release of drug.
According to other advantages of certain preferred embodiments of the invention, the particles can include drug dispersed therein prior to suspension into the carrier solution. Thus, in certain preferred embodiments a different drug can be provided in the particles for prolonged administration than the drug contained in the liquid medium. Further, according to certain preferred embodiments, the concentration of drug in the particles is such that when placed in a carrier solution having a different drug, the equilibrium between the two will be such that drug in the carrier solution will absorb into the particles. Thus, the particles will include different types of drug disposed therein for prolonged delivery.
According to other advantageous features of certain preferred embodiments of the invention, the specific equilibrium between drug in the particle and drug in the carrier liquid provides a specific amount of drug in the particle to be delivered over a specific duration when administered to the ocular area.
Methods for making the drug delivery system and methods of treating the eye using the drug delivery system are also provided.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.